The use of photonic integrated circuits, e.g. ring resonator sensors in high index contrast media, for biological and chemical sensing is well established. The high sensitivity of this technique to surface phenomena makes it ideal for use in real-time and label-free biosensors where very small changes in refractive index must be detected. Driven by the vision of a laboratory on a chip and its impact in numerous applications such as detection, bio sensing, kinetic and binding studies and point-of-care diagnostics, extensive work has been done to develop these miniature photonic integrated biosensors. In the past decade, several integrated optical sensors have been demonstrated, mainly using ring resonator sensors, where the detection of biomolecular interaction happens by tracking the wavelength shift of one resonant ring resonator mode.
Biomolecular interaction between a receptor molecule, previously deposited on a waveguide surface, and its complementary analyte, produces a change in refractive index at the sensor surface that induces a variation in the optical properties of the guided light via the evanescent field. A biomolecular layer can be optically modeled as a uniform layer with a certain thickness tL and a certain refractive index nL as is shown in FIG. 2. Most biosensing techniques cannot distinguish between thickness tL and refractive index nL of the binding layer on top of the biosensor, and the output is linked to a combination of these parameters or to another calibration parameter such as the molecular concentration.
In today's biological experiments performed on integrated biosensors, usually only one parameter is measured, being the resonance wavelength shift of the TE00 or TM00 resonating mode when biomolecular interaction occurs.
In one system making use of both TE and TM mode responses, an interferometer-based sensor constructed from two optical waveguides stacked on top of each other and an array photodiode is shown in FIG. 1, left drawing. When polarized light (TM) is introduced to the end of the stack, single mode excitations in sensing and reference waveguides are formed and propagate through the structure. At the output, they form the well-known pattern of Youngs interference fringes on an array photodiode. On exposing the sensing waveguide to a biomolecule that attaches to it, the phase will change in the sensing waveguide while the effective index of the reference waveguide does not change. Monitoring the relative phase position of the fringe pattern will reveal the TM output. Subsequently, a second polarization of light (TE) is introduced into the waveguide stack. As explained, this responds differently to biomolecule adsorption or removal, and provides a second independent measurement. For each polarization there are an infinite number of refractive index/film thickness combinations that will produce the observed effect. However, when both polarizations are taken together a unique solution is resolved.
However, DPI as available today is not a high throughput technique and without miniaturization it does not lend itself to the levels of multiplexing necessary for drug discovery. This system handles only a very limited number of parallel measurements (currently 2), since the optical input and output signals are coupled via the edges of the waveguide chip and different channels need to be straight, long, and well separated as is shown in FIG. 1. Moreover, the polarizations are sequentially measured due to the buried interferometric design.